Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas.
Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas.
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DOI：
10.1177/1947601911431081
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发表时间：
2011-08-01
期刊：
影响因子：
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通讯作者：
Molloy, Peter L
中科院分区：
文献类型：
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作者：
Graham, Lloyd D;Pedersen, Susanne K;Molloy, Peter L
一个未被鉴定的基因(chR16：hCG_1815491)，现在被称为结直肠癌差异表达(基因符号CRNDE)，在结直肠癌的早期就被激活。该基因与任何已知的蛋白质编码基因无关。对454个组织样本(发现)和68个以前未检测的样本(验证)的微阵列分析显示，CRNDE在90%的结直肠腺瘤和腺癌中表达升高。这些发现被外显子微阵列研究和RT-PCR检测所证实和扩展。用5‘-RACE方法鉴定了CaCo2和HCT116细胞中的CRNDE转录起始点。结直肠癌细胞系和结直肠组织中的主要转录异构体为CRNDE-a、-b、-d、-e、-f、-h和-j。除CRNDE-d外，已知的CRNDE剪接变异体在肿瘤大肠组织中上调；仅CRNDE-h的表达水平对腺瘤的敏感度和特异度分别为95%和96%。定量RT-PCR检测15例结直肠癌患者中13例(87%)血浆CRNDE-h RNA水平为阳性(阈值为2(-DeltaCt)=2.8)，而15例健康人中仅1例(7%)阳性。我们的结论是，单个CRNDE转录本有望作为组织和血浆生物标记物，潜在地对结直肠腺瘤和癌症表现出高度的敏感性和特异性。
An uncharacterized gene locus (Chr16:hCG_1815491), now named colorectal neoplasia differentially expressed (gene symbol CRNDE), is activated early in colorectal neoplasia. The locus is unrelated to any known protein-coding gene. Microarray analysis of 454 tissue specimens (discovery) and 68 previously untested specimens (validation) showed elevated expression of CRNDE in >90% of colorectal adenomas and adenocarcinomas. These findings were confirmed and extended by exon microarray studies and RT-PCR assays. CRNDE transcription start sites were identified in CaCo2 and HCT116 cells by 5'-RACE. The major transcript isoforms in colorectal cancer (CRC) cell lines and colorectal tissue are CRNDE-a, -b, -d, -e, -f, -h, and -j. Except for CRNDE-d, the known CRNDE splice variants are upregulated in neoplastic colorectal tissue; expression levels for CRNDE-h alone demonstrate a sensitivity of 95% and specificity of 96% for adenoma versus normal tissue. A quantitative RT-PCR assay measuring CRNDE-h RNA levels in plasma was (with a threshold of 2(-DeltaCt) = 2.8) positive for 13 of 15 CRC patients (87%) but only 1 of 15 healthy individuals (7%). We conclude that individual CRNDE transcripts show promise as tissue and plasma biomarkers, potentially exhibiting high sensitivity and specificity for colorectal adenomas and cancers.